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. 1995 Mar 28;92(7):2577–2581. doi: 10.1073/pnas.92.7.2577

Combination gene therapy for liver metastasis of colon carcinoma in vivo.

S H Chen 1, X H Chen 1, Y Wang 1, K Kosai 1, M J Finegold 1, S S Rich 1, S L Woo 1
PMCID: PMC42261  PMID: 7708688

Abstract

The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barba D., Hardin J., Sadelain M., Gage F. H. Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4348–4352. doi: 10.1073/pnas.91.10.4348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caruso M., Panis Y., Gagandeep S., Houssin D., Salzmann J. L., Klatzmann D. Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7024–7028. doi: 10.1073/pnas.90.15.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen S. H., Shine H. D., Goodman J. C., Grossman R. G., Woo S. L. Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3054–3057. doi: 10.1073/pnas.91.8.3054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colombo M. P., Ferrari G., Stoppacciaro A., Parenza M., Rodolfo M., Mavilio F., Parmiani G. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991 Apr 1;173(4):889–897. doi: 10.1084/jem.173.4.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corbett T. H., Griswold D. P., Jr, Roberts B. J., Peckham J. C., Schabel F. M., Jr Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975 Sep;35(9):2434–2439. [PubMed] [Google Scholar]
  6. Culver K. W., Ram Z., Wallbridge S., Ishii H., Oldfield E. H., Blaese R. M. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science. 1992 Jun 12;256(5063):1550–1552. doi: 10.1126/science.1317968. [DOI] [PubMed] [Google Scholar]
  7. Dranoff G., Jaffee E., Lazenby A., Golumbek P., Levitsky H., Brose K., Jackson V., Hamada H., Pardoll D., Mulligan R. C. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539–3543. doi: 10.1073/pnas.90.8.3539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ezzeddine Z. D., Martuza R. L., Platika D., Short M. P., Malick A., Choi B., Breakefield X. O. Selective killing of glioma cells in culture and in vivo by retrovirus transfer of the herpes simplex virus thymidine kinase gene. New Biol. 1991 Jun;3(6):608–614. [PubMed] [Google Scholar]
  9. Fearon E. R., Pardoll D. M., Itaya T., Golumbek P., Levitsky H. I., Simons J. W., Karasuyama H., Vogelstein B., Frost P. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell. 1990 Feb 9;60(3):397–403. doi: 10.1016/0092-8674(90)90591-2. [DOI] [PubMed] [Google Scholar]
  10. Gansbacher B., Zier K., Daniels B., Cronin K., Bannerji R., Gilboa E. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med. 1990 Oct 1;172(4):1217–1224. doi: 10.1084/jem.172.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Golumbek P. T., Lazenby A. J., Levitsky H. I., Jaffee L. M., Karasuyama H., Baker M., Pardoll D. M. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science. 1991 Nov 1;254(5032):713–716. doi: 10.1126/science.1948050. [DOI] [PubMed] [Google Scholar]
  12. Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum Gene Ther. 1992 Aug;3(4):399–410. doi: 10.1089/hum.1992.3.4-399. [DOI] [PubMed] [Google Scholar]
  13. Matthews T., Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 3):S490–S494. doi: 10.1093/clinids/10.supplement_3.s490. [DOI] [PubMed] [Google Scholar]
  14. Moolten F. L. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 1986 Oct;46(10):5276–5281. [PubMed] [Google Scholar]
  15. Oldfield E. H., Ram Z., Culver K. W., Blaese R. M., DeVroom H. L., Anderson W. F. Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther. 1993 Feb;4(1):39–69. doi: 10.1089/hum.1993.4.1-39. [DOI] [PubMed] [Google Scholar]
  16. Ram Z., Culver K. W., Walbridge S., Blaese R. M., Oldfield E. H. In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 1993 Jan 1;53(1):83–88. [PubMed] [Google Scholar]
  17. Stoppacciaro A., Melani C., Parenza M., Mastracchio A., Bassi C., Baroni C., Parmiani G., Colombo M. P. Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma. J Exp Med. 1993 Jul 1;178(1):151–161. doi: 10.1084/jem.178.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stratford-Perricaudet L. D., Levrero M., Chasse J. F., Perricaudet M., Briand P. Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. Hum Gene Ther. 1990 Fall;1(3):241–256. doi: 10.1089/hum.1990.1.3-241. [DOI] [PubMed] [Google Scholar]
  19. Takamiya Y., Short M. P., Moolten F. L., Fleet C., Mineta T., Breakefield X. O., Martuza R. L. An experimental model of retrovirus gene therapy for malignant brain tumors. J Neurosurg. 1993 Jul;79(1):104–110. doi: 10.3171/jns.1993.79.1.0104. [DOI] [PubMed] [Google Scholar]

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